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April 3, 2026Open Access

Anti-Ma2 Paraneoplastic Encephalitis and Testicular Cancer: When the Hypothalamus Whispers—A Case Report and Systematic Review with Emphasis on Hypothalamic-Endocrine Dysfunction

Key Points

This research aims to describe the relationship between anti-Ma2 paraneoplastic encephalitis and testicular cancer, particularly focusing on hypothalamic dysfunction.
Presented a case report of a 21-year-old male with anti-Ma2 PLE and testicular cancer.
Conducted a systematic literature review following PRISMA guidelines.
Included studies reporting on anti-Ma2 antibody positive cases associated with testicular tumors.
Used dynamic endocrine testing to evaluate hormone levels and diagnose conditions.
Identified 11 studies reporting 38 patients with anti-Ma2-associated PLE and testicular cancer.
16 patients (42%) had hypothalamic or diencephalic involvement.
Only four cases explicitly reported endocrine manifestations.
Two prior reports mentioned central diabetes insipidus without detailed diagnostics.

Abstract

Background: Paraneoplastic limbic encephalitis (PLE) with anti-Ma2 antibodies is a rare immune-mediated disorder associated with testicular cancer, particularly in young males. While neurological manifestations are well documented, hypothalamic–pituitary dysfunctions remain underreported. We present a case of anti-Ma2 PLE associated with testicular cancer together with a systematic review of PLE associated with testicular cancer, selectively restricted to anti-Ma2 positive cases and focusing on hypothalamic–endocrine involvement. Case presentation: We describe a 21-year-old male diagnosed with anti-Ma2 PLE and intratubular germ cell neoplasia of the right testis. He underwent orchifunicolectomy and immunosuppressive therapy with neurological improvement. Four years later, he developed new-onset temporal seizures, decreased libido, and a polyuria–polydipsia syndrome. Dynamic endocrine testing, including a water deprivation test and copeptin measurement, supported a diagnosis of partial central diabetes insipidus (CDI). Methods: A systematic literature review was performed in accordance with PRISMA guidelines. PubMed was searched using predefined keywords without time restriction. Studies reporting PLE associated with testicular tumors in humans with confirmed anti-Ma2 antibody positivity were included. Results: Eleven studies were included, reporting a total of 38 patients with anti-Ma2-associated PLE and testicular cancer. Hypothalamic or diencephalic involvement was described in 16 patients (42.0%), while endocrine manifestations were explicitly reported in four cases. Only two previous reports mentioned CDI, without detailed diagnostic evaluation. Conclusions: This study highlights the importance of recognizing hypothalamic-endocrine manifestations in PLE. In patients presenting with polydipsia and polyuria, CDI should be carefully differentiated from primary polydipsia using dynamic testing. Hypothalamic involvement may emerge years after tumor treatment, warranting long-term endocrine surveillance.

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